In the treatment of diabetes, current subcutaneous insulin therapy is limited by the delayed time of onset and time of peak action for the insulin, inability to accommodate changing insulin requirements, e.g. during exercise or meals, and by the large inter- and intra-subject coefficient of variation of absorption and insulin action. Oral delivery of insulin would overcome many of the disadvantages of the subcutaneous delivery system.
The inability of subcutaneous insulin delivery to effectively and safely control glucose levels has encouraged exploration of alternate, less painful methods of delivery that might provide a faster rate of insulin absorption and a relatively short half life. Oral administration of insulin to treat diabetes is likely to be attractive because of its virtual lack of toxicity and its inherent clinical applicability in the reduction in severity of lymphocytic infiltration of pancreatic islets. Furthermore, it has been shown that splenic T-cells from animals orally treated with insulin adoptively transfer protection against diabetes, which indicates that oral insulin generates active cellular mechanisms that suppress disease. Such results suggest that oral insulin affects diabetes and the pancreatic cellular inflammatory process and raises the possibility that oral administration of insulin may provide a new approach for the treatment of autoimmune diabetes.
As indicated, oral delivery of insulin would have many benefits. Oral delivery is also a preferred method of delivering many other therapeutic or pharmaceutical agents. In some instance, even nasal delivery is preferred from a patient point of view because it is not painful like subcutaneous administration and it may be easily self-administered. Nasal delivery of therapeutic agents has the disadvantage that the amount of agent (dose) delivered varies from one dose to another, for a variety of reasons. For example, the lining of the nose is sensitive and sneezing or dripping as a result of irritation of the lining causes loss of usable therapeutic agent. Oral delivery of therapeutic or pharmaceutical agents overcome these difficulties. Even so, if a nasal delivery method is desired, an improved formulation would be helpful.
Effective oral delivery of a pharmaceutical agent requires that the agent has sufficient solubility in the stomach and intestinal lumen and the ability to pass through the intestinal wall. Many peptidic drugs have extremely poor absorption in the gastrointestinal tract and tend to degrade quickly. For example insulin, when introduced orally, has extremely poor absorption in the gastrointestinal tract, tends to degrade quickly, and thus has no metabolic effect on blood glucose levels.
M. Kidron, H. Bar-on, E. M. Berry and E. Ziv in Life Sciences, vol 29, pp 803-9 (1981) and vol 31, pp 2837-41 (1982) have experimented in small animals, with surgical delivery of insulin to the small intestine of a composition of 5 wt. % of an absorption enhancer, e.g. sodium cholate, 2 wt% soyabean trypsin inhibitor and 15 IU of insulin. Such a composition had a metabolic effect on blood sugar level, i.e reduced the blood sugar level by about 30%. However a large amount of insulin was required to produce this effect. The method is obviously not practical in humans and the amount of insulin required would be prohibitively expensive.
A composition which provides effective and practical oral or for some compositions, nasal delivery of pharmaceutical agents has been found.